Juniperonic Acid Biosynthesis is Essential in Caenorhabditis Elegans Lacking ?6 Desaturase (fat-3) and Generates New ?-3 Endocannabinoids.

ABSTRACT: In eukaryotes, the C20:4 polyunsaturated fatty acid arachidonic acid (AA) plays important roles as a phospholipid component, signaling molecule and precursor of the endocannabinoid-prostanoid axis. Accordingly, the absence of AA causes detrimental effects. Here, compensatory mechanisms involved in AA deficiency in Caenorhabditis elegans were investigated. We show that the ?-3 C20:4 polyunsaturated fatty acid juniperonic acid (JuA) is generated in the C. elegansfat-3(wa22) mutant, which lacks ?6 desaturase activity and cannot generate AA and ?-3 AA. JuA partially rescued the loss of function of AA in growth and development. Additionally, we observed that supplementation of AA and ?-3 AA modulates lifespan of fat-3(wa22) mutants. We described a feasible biosynthetic pathway that leads to the generation of JuA from ?-linoleic acid (ALA) via elongases ELO-1/2 and ?5 desaturase which is rate-limiting. Employing liquid chromatography mass spectrometry (LC-MS/MS), we identified endocannabinoid-like ethanolamine and glycerol derivatives of JuA and ?-3 AA. Like classical endocannabinoids, these lipids exhibited binding interactions with NPR-32, a G protein coupled receptor (GPCR) shown to act as endocannabinoid receptor in C. elegans. Our study suggests that the eicosatetraenoic acids AA, ?-3 AA and JuA share similar biological functions. This biosynthetic plasticity of eicosatetraenoic acids observed in C. elegans uncovers a possible biological role of JuA and associated ?-3 endocannabinoids in ?6 desaturase deficiencies, highlighting the importance of ALA.

SUBMITTER: Guha S 

PROVIDER: S-EPMC7564282 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature